scholarly journals Lipid-soluble components in cigarette smoke induce mitochondrial production of reactive oxygen species in lung epithelial cells

2009 ◽  
Vol 297 (1) ◽  
pp. L109-L114 ◽  
Author(s):  
Marco van der Toorn ◽  
Delaram Rezayat ◽  
Henk F. Kauffman ◽  
Stephan J. L. Bakker ◽  
Rijk O. B. Gans ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Epithelial Cells ◽  
Cigarette Smoke ◽  
Gaseous Phase ◽  
Mitochondrial Function ◽  
A549 Cells ◽  
Reactive Oxygen ◽  
Airway Epithelial Cells ◽  
Oxygen Species ◽  
Airway Epithelial

Reactive oxygen species (ROS) present in cigarette smoke (CS) are thought to contribute to the development of COPD. Although CS-ROS can hardly enter airway epithelial cells, and certainly not the circulation, systemic levels of ROS have been found to be elevated in COPD patients. We hypothesize that lipophilic components present in CS can enter airway epithelial cells and increase intracellular ROS production by disturbing mitochondrial function. Different airway epithelial cells were exposed to CS extract (CSE), hexane-treated CSE (CSE without lipophilic components), gaseous-phase CS, and water-filtered CS (gaseous-phase CS without ROS). Mitochondrial membrane potential (Δψm) and ATP levels were assessed using the bronchial epithelial cell line Beas-2b. ROS generation measured directly by DCF fluorescence and indirectly by measuring free thiol groups (-SH) upon exposure to CS was assessed using lung alveolar epithelial cells devoid of functional mitochondria (A549-ρ0), with normal A549 cells serving as controls. In Beas-2b cells, CSE (4 h) caused a dose-dependent decrease in Δψm and ATP levels, whereas hexane-treated CSE did not. DCF fluorescence in A549 cells increased in response to CSE, whereas this was not the case in A549-ρ0 cells. Exposure of A549 cells to CS resulted in a rapid decrease in free -SH, whereas exposure to ROS-depleted CS only resulted in a delayed decrease. This delayed decrease was less pronounced in A549-ρ0 cells. Lipophilic components in CS disturb mitochondrial function, which contributes to increased intracellular generation of ROS. Our results are of importance in understanding the systemic effects of smoking observed in patients with COPD.

Superoxide dismutase moderates basal and induced bacterial adherence and interleukin-8 expression in airway epithelial cells

2004 ◽  
Vol 287 (6) ◽  
pp. L1199-L1206 ◽  
Author(s):  
Yuko Arita ◽  
Ansamma Joseph ◽  
Hshi-Chi Koo ◽  
Yuchi Li ◽  
Thomas A. Palaia ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Superoxide Dismutase ◽  
Epithelial Cells ◽  
A549 Cells ◽  
Reactive Oxygen ◽  
Bacterial Adherence ◽  
Interleukin 8 ◽  
Lung Epithelial Cells ◽  
Oxygen Species ◽  
Airway Epithelial

Bacterial infection of the tracheobronchial tree is a frequent, serious complication in patients receiving treatment with oxygen and mechanical ventilation, resulting in increased morbidity and mortality. Using human airway epithelial cell culture models, we examined the effect of hyperoxia on bacterial adherence and the expression of interleukin-8 (IL-8), an important mediator involved in the inflammatory process. A 24-h exposure to 95% O2increased Pseudomonas aeruginosa (PA) adherence 57% in A549 cells ( P < 0.01) and 115% in 16HBE cells ( P < 0.01) but had little effect on Staphylococcus aureus (SA) adherence. Exposure to hyperoxia, followed by a 1-h incubation with SA, further enhanced PA adherence ( P < 0.01), suggesting that hyperoxia and SA colonization may enhance the susceptibility of lung epithelial cells to gram-negative infections. IL-8 expression was also increased in cells exposed to both hyperoxia and PA. Stable or transient overexpression of manganese superoxide dismutase reduced both basal and stimulated levels of PA adherence and IL-8 levels in response to exposure to either hyperoxia or PA. These data indicate that hyperoxia increases susceptibility to infection and that the pathways are mediated by reactive oxygen species. Therapeutic intervention strategies designed to prevent accumulation of intracellular reactive oxygen species may reduce opportunistic pulmonary infections.

scholarly journals Nlrx1-Regulated Defense and Metabolic Responses to Aspergillus fumigatus Are Morphotype and Cell Type Specific

2021 ◽  
Vol 12 ◽  
Author(s):  
Bridget Kastelberg ◽  
Tariq Ayubi ◽  
Nuria Tubau-Juni ◽  
Andrew Leber ◽  
Raquel Hontecillas ◽  
...  
Keyword(s):  
Reactive Oxygen Species ◽  
Bone Marrow ◽  
Epithelial Cells ◽  
Aspergillus Fumigatus ◽  
Airway Epithelial Cells ◽  
Oxygen Species ◽  
Airway Epithelial ◽  
Cell Type ◽  
Immune Signaling ◽  
Cell Type Specific

The Nlr family member X1 (Nlrx1) is an immuno-metabolic hub involved in mediating effective responses to virus, bacteria, fungi, cancer, and auto-immune diseases. We have previously shown that Nlrx1 is a critical regulator of immune signaling and mortality in several models of pulmonary fungal infection using the clinically relevant fungus Aspergillus fumigatus. In the absence of Nlrx1, hosts produce an enhanced Th2 response primarily by CD103+ dendritic cell populations resulting in enhanced mortality via immunopathogenesis as well as enhanced fungal burden. Here, we present our subsequent efforts showcasing loss of Nlrx1 resulting in a decreased ability of host cells to process A. fumigatus conidia in a cell-type-specific manner by BEAS-2B airway epithelial cells, alveolar macrophages, bone marrow-derived macrophages, but not bone marrow-derived neutrophils. Furthermore, loss of Nlrx1 results in a diminished ability to generate superoxide and/or generic reactive oxygen species during specific responses to fungal PAMPs, conidia, and hyphae. Analysis of glycolysis and mitochondrial function suggests that Nlrx1 is needed to appropriately shut down glycolysis in response to A. fumigatus conidia and increase glycolysis in response to hyphae in BEAS-2B cells. Blocking glycolysis and pentose phosphate pathway (PPP) via 2-DG and NADPH production through glucose-6-phosphate dehydrogenase inhibitor resulted in significantly diminished conidial processing in wild-type BEAS-2B cells to the levels of Nlrx1-deficient BEAS-2B cells. Our findings suggest a need for airway epithelial cells to generate NADPH for reactive oxygen species production in response to conidia via PPP. In context to fungal pulmonary infections, our results show that Nlrx1 plays significant roles in host defense via PPP modulation of several aspects of metabolism, particularly glycolysis, to facilitate conidia processing in addition to its critical role in regulating immune signaling.

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